Targeting PRMT5 as a Novel Radiosensitization Approach for Primary and Recurrent Prostate Cancer Treatment

Prostate cancer is the second leading cause of cancer death in the United States. Although radiotherapy (RT) is one of the two curative treatments for prostate cancer patients, approximately 10 of low-risk cancer patients and 30-60 of high-risk prostate cancer patients experience biochemical recurrence within five years, among them 20 die in 10 years. The proposed research is based on the hypothesis that targeting protein arginine methyltransferase 5(PRMT5) can sensitize primary and recurrent prostate cancer cells to RT. During the grant period, we have made significant progression in our understanding f how PRMT5 overexpression contributes to both intrinsic and acquired radio resistance in prostate cancer. First, PRMT5 is overexpressed in prostate cancer and its expression correlates positively with the expression of the androgen receptor (AR). Mechanistically PRMT5 epigenetically activates transcription of AR.